Self-oligomerization of NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer's disease amyloid, observed in the presence of a C-terminal A beta fragment (residues 25-35).
NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer's disease (AD) amyloid, also known as alpha-synuclein, was suggested to seed amyloid plaque formation in AD by stimulating A beta aggregation. We have demonstrated that NACP experienced self-oligomerization only in the presence of a modified A beta fragment (A beta25-35) by using dicyclohexylcarbodiimide. This NACP oligomerization, appearing as a discrete ladder on a Tricine SDS-PAGE, was not observed with other A beta peptides such as the reverse peptide A beta35-25 and A beta1-40, indicating this process was specific not only for the C-terminal peptide sequence of the A beta but also for its orientation. It might be, therefore, suggested that the NACP self-oligomers formed only in the presence of a N-terminally truncated A beta peptide could act as a nucleation center for plaque formation during AD development.
Paik
S R
SR
Department of Biochemistry, College of Medicine, Inha University, Inchon, South Korea. srpaik@dragon.inha.ac.kr
Lee
J H
JH
Kim
D H
DH
Chang
C S
CS
Kim
Y S
YS
D000544:Alzheimer Disease; D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001667:Binding, Competitive; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D000682:Amyloid; D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; C074636:amyloid beta-protein (25-35); D004024:Dicyclohexylcarbodiimide